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Nadine Cerf-Bensussan: Understanding Intestinal Barrier Disorders

Trained in pediatrics and immunology, Nadine Cerf-Bensussan studies the intestinal immune system as well as its role in human pathology. She obtained funding from the European Research Council in 2013 (ERC Advanced Grant) as head of a team at the Imagine Institute for Genetic Diseases. This funding will notably help her to learn more about rare and very severe genetic diseases, which affect how this barrier works, in order to improve diagnosis and treatment.

The intestinal immune system was not a popular subject when you began to study it. What has drawn you down this path?

Nadine Cerf-Bensussan

During my first hospital internship, I was fascinated by the way in which Claude Griscelli, pediatrician and immunologist at Necker Hospital, approached the immune system through the study of its dysfunctions. In turn, he identified diagnostic tools and logical therapeutic strategies. I joined his team to work on intestinal immunity in humans, while Delphine Guy-Grand studied it in mice.

It is true that at the time, immunologists had little or no interest in the intestines. Yet, it seemed obvious to me that the intestine must be monitored very closely by the immune system, with its 300 m2 in contact with billions of germs and since it is bombarded daily by food antigens. The subject fascinated me and led me to write a Ph.D. thesis, partly at Harvard and partly at Necker. Then, I continued to work on intestinal immunity and disorders associated with its dysfunction, at an Inserm laboratory.

Since 2003 and based on work initiated by microbiologists from François Taddei’s team, our team is also committed to elucidating the interactions between the host and the enormous microbial community hosted in the intestines of mice. In 2012, I was invited to join the newly formed Imagine Institute. This prompted me to apply my expertise to the study of genetic intestinal diseases in children, including those who are prone to dysfunctional interactions with intestinal bacteria.

How do these various aspects relate to your research project funded by the ERC?

The project aims to define the factors essential to the development of an efficient and well-regulated intestinal barrier in humans. The ultimate purpose is to identify the relevant therapeutic approaches should a dysfunction occur. 

Today, we know that this barrier is built by a complex and very dynamic dialog between the immune system and the bacteria of the microbiota. In particular, we have isolated a bacterium that plays an essential role in the maturation of this barrier in mice. Our intention is to discover whether this bacterium also exists in humans and how it contributes to the development of the intestinal barrier.

Over the past 15 years, a large number of genes involved in the makeup of the intestinal barrier have been identified in mice. The study of patients with rare genetic gastrointestinal diseases should help to precisely identify those that are essential in humans. In turn, precise identification of the deficient gene and the cell type affected by this deficit, in each patient, should help in selecting the most suitable therapeutic strategy for each patient. This work is part of the translational research approach developed for children's genetic diseases at the Imagine Institute. It is carried out in close cooperation with Necker pediatric gastroenterologists and other pediatric gastroenterology departments that have agreed to participate in the Immunobiota network established through the ERC funding.

How has the ERC grant been used for your research?

This funding program is a fantastic opportunity in the life of a researcher. It offers freedom and an exceptional boost that is otherwise hard to find due to the current fragmentation of funding. I would not have dared to apply if Inserm had not expressly asked me to do so! This incentive occurred as I was about to join Imagine, allowing me to plan an ambitious and innovative 5-year program. ERC funding has also allowed me to hire talented young people, who bring skills complementary to mine to the project. I am also very proud that my ERC grant has allowed me to finance Pamela Schnupf, a young microbiology researcher who has joined Inserm this year. Her project involves the design of effective vaccines against enteropathogens, such as Shigella. Therefore, she intends to use a powerful bacterial immunostimulant that we helped characterize together.

Learn more about Nadine Cerf-Bensussan and her work
Nadine Cerf-Bensussan heads the Laboratory of Intestinal Immunity within Inserm Unit 1163/Université Paris-Descartes, at the Imagine Institute for Genetic Diseases. She received the Inserm Research Prize in 2014.

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